Advances in immunogenetics have established that T lymphocytes can be categorized into different sets of cells that are separately and coordinately programmed for particular surface phenotypes and immune functions. Earlier it was shown that lymphoid tissues have prescribed compartments for the major classes of lymphocytes, T and B; this regional deployment can be viewed in terms of necessity for collaborative interactions between separately programmed lymphocyte populations. It can now be determined experimentally whether discriminative regional deployment is also a feature of T cell sets identified by their immunogenetic surface phenotypes. In a pilot study we have shown that it is feasible to trace separate life histories of different T cell sets in vivo. The two methods used were: 1. histological study of B mice reconstituted with selected Lyt-1 or Lyt-23 sets, and 2. migration patterns of selected radiolabeled Lyt-1 or Lyt-23 cells in syngeneic recipients. We also have some confirmatory evidence in hr/hr mice, in that their lymphoid tissues show a histological pattern that is predictable from an hr-associated selective Lyt set deficiency which is being investigated. We propose to exploit this combination of immunogenetic and micro-anatomical methods, in Lyt and other systems (e.g., the Qa group), and in other immunologically aberrant mutant mice, with two main objectives: 1. to ascertain to what extent, and how, collaborative cellular interactions required for immune responses are related to the organization of lymphocyte populations both inter se and in relation to lymphoid stromata, and 2. to propound principles for the rational relation of changes in lymphoid histology to defined categories of immuno-deficiency.